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Characterization of a new renal cell carcinoma bone metastasis mouse model

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Abstract

Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently and becomes more and more prevalent presumably because survival times among patients with disseminated cancers are increasing. Patients with bone metastases from renal cell carcinoma suffer from severe pain, nerve compression syndromes and pathologic fractures. Very little is known about the mechanisms of skeletal metastases of RCC. Thus, to better understand the molecular mechanism of renal cell cancer (RCC) bone metastasis, it is crucial to develop new animal models. We have established a new animal model of RCC metastasis to bone by inoculation of human 786-O/luciferase cells into the left cardiac ventricle of athymic nude mice. The animals developed aggressive osteolytic bone destruction as monitored by radiography and micro-CT-scans with the mean endpoint at 62 ± 8 days. The extensive bone destruction observed was comparable to the clinical setting and mainly occurred in hind limbs, forelimbs and the spine. The tumors were primarily located within the bone and resulted in destruction of cortical bone. No soft tissue metastases were detected by BLI or histomorphometry. To increase the bone-metastatic potential of the 786-O cell line, an in vivo selection was done yielding a subpopulation causing osteolytic lesions with the mean endpoint of 47 ± 3 days. The selected subline secreted more proangiogenic factors VEGF and bFGF in vitro compared to the parental cell line suggesting that these tumors are highly vascular. This model provides a reliable reproduction of the clinical situation and therefore, is suitable for designing and evaluating more effective treatments for RCC bone metastasis.

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Abbreviations

RCC:

Renal cell carcinoma

VEGF:

Vascular endothelial growth factor

bFGF:

Basic fibroblast growth factor

luc:

Luciferase

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Acknowledgements

We thank Bernd Hartmann, Ina Neumann, Christine Morgenroth, Meike Fehder, Wilhelm Ebel, Andreas Jung and Julia Meier for excellent technical assistance.

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Author notes

  1. Sanna-Maria Käkönen

    Present address: Amgen AB Finland, Espoo, Finland

Authors and Affiliations

  1. Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Schering Pharma AG, 13342, Berlin, Germany

    Anne Strube, Dominik Mumberg, Arne Scholz & Sanna-Maria Käkönen

  2. Global Drug Discovery, TRG Diagnostic, Bayer Schering Pharma AG, Berlin, Germany

    Elizaveta Stepina & Peter Hauff

  3. Department of Biology, Chemistry and Pharmacy, Free University Berlin, Berlin, Germany

    Anne Strube

  4. Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland

    Sanna-Maria Käkönen

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  1. Anne Strube
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Correspondence to Dominik Mumberg.

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Strube, A., Stepina, E., Mumberg, D. et al. Characterization of a new renal cell carcinoma bone metastasis mouse model. Clin Exp Metastasis 27, 319–330 (2010). https://doi.org/10.1007/s10585-010-9329-9

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  • DOI: https://doi.org/10.1007/s10585-010-9329-9

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